Various strategies have been developed to generate bispecific molecules capable of T cell recruitment to mediate tumor cell killing. However, most efforts to produce such molecules have been limited because of inefficient production and poor stability properties. To address these problems, an Fv-derived strategy based on a covalently linked, bispecific heterodimeric diabody structure, also known as dual-affinity re-targeting (DART®) proteins, has been developed (US Patent Application Publications Nos. 2007/0004909, 2009/0060910, and 2010/0174053).
There remains a need for bispecific heterodimeric diabodies that overcome the challenges associated with the generation of bispecific antibodies and provide highly specific and potent agents that bind to tumor cells expressing a target antigen and recruit and activate T cells through CD3 activation, resulting in an innovative and effective treatment for cancer.